51. Structure and RNA binding of the third KH domain of poly(C)-binding protein 1
- Author
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Julian P. Vivian, Corrine Joy Porter, Jacqueline A. Wilce, M Sidiqi, Matthew C.J. Wilce, Peter J. Leedman, and Andrew Barker
- Subjects
Models, Molecular ,Untranslated region ,Messenger RNA ,Binding Sites ,Stereochemistry ,Binding protein ,Molecular Sequence Data ,Oligonucleotides ,RNA-Binding Proteins ,RNA ,RNA-binding protein ,Surface Plasmon Resonance ,Biology ,Molecular biology ,Article ,KH domain ,Protein Structure, Tertiary ,Poly C ,Genetics ,Amino Acid Sequence ,Binding site ,3' Untranslated Regions ,Sequence Alignment ,Binding domain - Abstract
Poly(C)-binding proteins (CPs) are important regulators of mRNA stability and translational regulation. They recognize C-rich RNA through their triple KH (hn RNP K homology) domain structures and are thought to carry out their function though direct protection of mRNA sites as well as through interactions with other RNA-binding proteins. We report the crystallographically derived structure of the third domain of alphaCP1 to 2.1 A resolution. alphaCP1-KH3 assumes a classical type I KH domain fold with a triple-stranded beta-sheet held against a three-helix cluster in a betaalphaalphabetabetaalpha configuration. Its binding affinity to an RNA sequence from the 3'-untranslated region (3'-UTR) of androgen receptor mRNA was determined using surface plasmon resonance, giving a K(d) of 4.37 microM, which is indicative of intermediate binding. A model of alphaCP1-KH3 with poly(C)-RNA was generated by homology to a recently reported RNA-bound KH domain structure and suggests the molecular basis for oligonucleotide binding and poly(C)-RNA specificity.
- Published
- 2005